Diminished glucose tolerance is a characteristic of the elderly individual. However, its metabolic basis and health significance remains unclear. In these studies we are exploring quantitative aspects of whole body glucose metabolism with the aid of stable isotopes (13C,2H). These techniques allow similar studies to be conducted in young adults and thus provides an opportunity to examine, in detail, responses of glucose metabolism (endogenous production, oxidation, recycling, disappearance) of various stimuli (diet, glucose infusion) in subjects of increasing adult age. Studies on the effects of variable levels of glucose infusion in a group of healthy elderly subjects (70-80 yr) have been undertaken and the analytical work is currently incomplete. Plans are to expand these studies to incorporate an examination of the interrelations between glucose and amino acid metabolism in order to develop a more comprehensive picture of the age-dependent changes in human glucose metabolism. These studies will also involve use of amino acids labeled with stable isotopes, principally, leucine-1-13C and lysine-1-13C.